Macromolecular crystallography may be used both in academia and industry for structural analysis of biological molecules and to help in the development of therapeutic and other bioactive molecules. For this purpose samples are mixed with solutions containing components that are likely to induce crystal formation in multi-cell plates. Crystals need to be exposed to powerful x-ray beams to extract structural information.
Multi-cell plates used for macromolecular crystallography, e.g. for protein crystallisation, comprise a plurality of cells. Different samples with biological material may be incubated in different crystallization solutions into the different cells or chambers of the multi-cell plate. Crystals may take from hours to several weeks to appear, during which time multi-cell plates are stored at constant temperature and inspected regularly under a microscope with visible or UV light.
Crystals may be exposed to x-rays directly in multi-cell plates. However this produces a high level of background due to interference produced by the material of the multi-cell plate, decreasing the quality of the data. More often crystals are extracted out of the multi-well plate with a specific tool (a cryo-loop) working under a microscope. This eliminates the interference from the multi-cell plate material and reduces the amount of crystallization solution around the crystal that may also interfere with the measurement. X-ray experiments are often performed at cryogenic temperature (100 Kelvin for example). Crystals are often also stored and transported at this temperature. Thus, it may often be necessary to provide the crystals with cryo protection for further storage, transport or for analysis, e.g. by x-ray diffraction. For this purpose each sample has to be removed from the plate and incubated with a solution containing a cryo protectant agent.
Furthermore, for some applications it may be necessary to deliver to the crystals additional components such as ligands. Also in this case samples, e.g. crystals, are extracted from the solution in which they grow and transferred to solutions containing those chemical agents. This process is also denoted as soaking (ligand soaking, heavy atom soaking etc).
The mentioned steps of crystal harvesting (crystal extraction) and processing require a significant amount of manpower and time, especially when large amounts of crystals needs to be tested or when large libraries of compound are assayed in the context of structure-guided design of bioactive molecules. Furthermore, due to the necessity of several manual steps the results of the analysis are dependent on the skills of the operator. Moreover, the samples, e.g. crystallized biological material, may be mechanically damaged by removing and displacing from the multi-cell plate.